The hexapeptide functionalized gold nanoparticles protect against sepsis-associated encephalopathy by forming specific protein corona and regulating macrophage activation
Sepsis-induced systemic inflammatory responses can often lead to brain dysfunction with impaired cognitive function and mobility, known as sepsis-associated encephalopathy (SAE). Currently, there are no effective pharmacological therapeutics to treat SAE. Herein, we demonstrated the hexapeptide func...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | Materials Today Bio |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425002637 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850049535670222848 |
|---|---|
| author | Zichen Song Hongguang Chen Wenfei Xu Xiaoye Zong Xiaoyu Wang Yuting Ji Jiameng Gong Mimi Pang Shan-Yu Fung Hong Yang Yonghao Yu |
| author_facet | Zichen Song Hongguang Chen Wenfei Xu Xiaoye Zong Xiaoyu Wang Yuting Ji Jiameng Gong Mimi Pang Shan-Yu Fung Hong Yang Yonghao Yu |
| author_sort | Zichen Song |
| collection | DOAJ |
| description | Sepsis-induced systemic inflammatory responses can often lead to brain dysfunction with impaired cognitive function and mobility, known as sepsis-associated encephalopathy (SAE). Currently, there are no effective pharmacological therapeutics to treat SAE. Herein, we demonstrated the hexapeptide functionalized gold nanoparticles P12 that reduced SAE in septic mice with a dual mechanism to down-regulate systemic inflammation. We found that intraperitoneally administered P12 could target macrophages and regulate their inflammatory responses to decrease systemic inflammation and improve mice's cognitive function and mobility with SAE. Depleting peritoneal macrophages diminished the neuroprotective effects of P12 in SAE mice, suggesting macrophages as the effector cells for the neuroprotection by P12. In addition, the proteomic analysis revealed that P12 was capable of sequestering specific circulating inflammatory proteins in the blood of septic mice by forming a protein corona, contributing to the suppression of systemic inflammation. We also found that the local administration of P12 directly to the brain parenchyma effectively inhibited microglia activation and neuroinflammation in mice with SAE. This study provides an insightful understanding of the function and mechanisms of action of P12 in regulating sepsis-associated systemic inflammation and presents a new drug-free nanotherapeutic approach to treat SAE. |
| format | Article |
| id | doaj-art-b0f332efe1e14ce986fcb8e1ef917d9b |
| institution | DOAJ |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-b0f332efe1e14ce986fcb8e1ef917d9b2025-08-20T02:53:41ZengElsevierMaterials Today Bio2590-00642025-06-013210170410.1016/j.mtbio.2025.101704The hexapeptide functionalized gold nanoparticles protect against sepsis-associated encephalopathy by forming specific protein corona and regulating macrophage activationZichen Song0Hongguang Chen1Wenfei Xu2Xiaoye Zong3Xiaoyu Wang4Yuting Ji5Jiameng Gong6Mimi Pang7Shan-Yu Fung8Hong Yang9Yonghao Yu10Department of Anesthesia, Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, NO. 154 Anshan Road, Tianjin 300052, ChinaDepartment of Anesthesia, Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, NO. 154 Anshan Road, Tianjin 300052, ChinaDepartment of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, ChinaDepartment of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, ChinaDepartment of Immunology and Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, ChinaDepartment of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, ChinaDepartment of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, ChinaDepartment of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, ChinaDepartment of Immunology and Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, ChinaDepartment of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China; Corresponding author.Department of Anesthesia, Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, NO. 154 Anshan Road, Tianjin 300052, China; Corresponding author.Sepsis-induced systemic inflammatory responses can often lead to brain dysfunction with impaired cognitive function and mobility, known as sepsis-associated encephalopathy (SAE). Currently, there are no effective pharmacological therapeutics to treat SAE. Herein, we demonstrated the hexapeptide functionalized gold nanoparticles P12 that reduced SAE in septic mice with a dual mechanism to down-regulate systemic inflammation. We found that intraperitoneally administered P12 could target macrophages and regulate their inflammatory responses to decrease systemic inflammation and improve mice's cognitive function and mobility with SAE. Depleting peritoneal macrophages diminished the neuroprotective effects of P12 in SAE mice, suggesting macrophages as the effector cells for the neuroprotection by P12. In addition, the proteomic analysis revealed that P12 was capable of sequestering specific circulating inflammatory proteins in the blood of septic mice by forming a protein corona, contributing to the suppression of systemic inflammation. We also found that the local administration of P12 directly to the brain parenchyma effectively inhibited microglia activation and neuroinflammation in mice with SAE. This study provides an insightful understanding of the function and mechanisms of action of P12 in regulating sepsis-associated systemic inflammation and presents a new drug-free nanotherapeutic approach to treat SAE.http://www.sciencedirect.com/science/article/pii/S2590006425002637Sepsis-associated encephalopathyBioactive nanoparticlesProtein coronaMonocyte/macrophageInflammation |
| spellingShingle | Zichen Song Hongguang Chen Wenfei Xu Xiaoye Zong Xiaoyu Wang Yuting Ji Jiameng Gong Mimi Pang Shan-Yu Fung Hong Yang Yonghao Yu The hexapeptide functionalized gold nanoparticles protect against sepsis-associated encephalopathy by forming specific protein corona and regulating macrophage activation Materials Today Bio Sepsis-associated encephalopathy Bioactive nanoparticles Protein corona Monocyte/macrophage Inflammation |
| title | The hexapeptide functionalized gold nanoparticles protect against sepsis-associated encephalopathy by forming specific protein corona and regulating macrophage activation |
| title_full | The hexapeptide functionalized gold nanoparticles protect against sepsis-associated encephalopathy by forming specific protein corona and regulating macrophage activation |
| title_fullStr | The hexapeptide functionalized gold nanoparticles protect against sepsis-associated encephalopathy by forming specific protein corona and regulating macrophage activation |
| title_full_unstemmed | The hexapeptide functionalized gold nanoparticles protect against sepsis-associated encephalopathy by forming specific protein corona and regulating macrophage activation |
| title_short | The hexapeptide functionalized gold nanoparticles protect against sepsis-associated encephalopathy by forming specific protein corona and regulating macrophage activation |
| title_sort | hexapeptide functionalized gold nanoparticles protect against sepsis associated encephalopathy by forming specific protein corona and regulating macrophage activation |
| topic | Sepsis-associated encephalopathy Bioactive nanoparticles Protein corona Monocyte/macrophage Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425002637 |
| work_keys_str_mv | AT zichensong thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT hongguangchen thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT wenfeixu thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT xiaoyezong thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT xiaoyuwang thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT yutingji thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT jiamenggong thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT mimipang thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT shanyufung thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT hongyang thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT yonghaoyu thehexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT zichensong hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT hongguangchen hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT wenfeixu hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT xiaoyezong hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT xiaoyuwang hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT yutingji hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT jiamenggong hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT mimipang hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT shanyufung hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT hongyang hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation AT yonghaoyu hexapeptidefunctionalizedgoldnanoparticlesprotectagainstsepsisassociatedencephalopathybyformingspecificproteincoronaandregulatingmacrophageactivation |